During an inspection of your firm located in Haw River, North Carolina, on November 11, 2011, through November 29, 2011, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures a line of ethylene oxide sterilizers and sterilizer accessories. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body.

Our inspection revealed that your firm's ethylene-oxide (EO) gas sterilizers and physical and chemical indicators are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) of these products in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g). These devices are also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. § 360(k). For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency [Title 21 Code of Federal Regulations, 807.81 (b)]. The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.

Additionally, under section 510 of the Act (21 U.S.C. § 360), manufacturers of medical devices are required to annually register with the FDA. In September 2007, section 510 of the Act was amended by the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110-85) to require domestic and foreign device establishments to submit their annual establishment registration and device listing information to FDA by electronic means [section 510(p) of the Act (21 U.S.C. § 360(p))] during the period beginning October 1st and ending December 31st of each year. Our records indicate that your firm has not fulfilled annual registration and listing requirements for fiscal year 2011.

Therefore all of your firm's devices are misbranded within the meaning of section 502(o) of the Act, 21 U.S.C. § 352(o), in that the devices were manufactured, prepared, propagated, compounded, or processed in an establishment not duly registered under section 510 of the Act, 21 U.S.C. § 360, and were not included in a list required by section 510(j) of the Act, 21 U.S.C. § 360(j).

Your firm should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the awarding of contracts.

Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (including any systemic corrective actions) that your firm has taken. If your firm's planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm's response should be comprehensive and address all violations included in this Warning Letter.

In addition, FDA noted nonconformances with regards to section 501(h) of the Act, 21 U.S.C. § 351(h), which are deficiencies within your firm's quality system pertaining to current good manufacturing practice requirements specified in the Quality System regulation found at 21 CFR Part 820. These nonconformities include, but are not limited to, the following:

1. Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designed unit, as required by 21 CFR 820.198(a). Specifically, FDA's review of complaint files found that your firm's complaint handling unit is not documenting adequate information on the customer feedback forms. Nor is it advancing reported customer dissatisfaction to a complaint unit as required in your firm's established procedures. For example:

a. CFF #S1171 and CFF #S1168, both related to reports of (EO) spills, which represent an MDR reportable event, were not evaluated for MDR reportability.b. CFF #S1177 indicates that a patient injury occurred; however, there is no follow up to the report that EO spilled on the user.c. CFF #S1168 indicates that an empty syringe was found by the user and the question was posed as to whether there is a danger to the operator. The distributor, HW Anderson Products of California, indicates that Andersen Sterilizers should be notified. However, the issue was not furthered investigated.

We reviewed your firm's response dated December 16, 2011, and conclude that it is not adequate. Your firm states that it will create an external feedback form as an attachment to the revised Feedback procedure. The form will be device specific and will include questionnaires that will assist in preliminary root cause analysis on all customer feedbacks received by your firm. The external feedback form was not provided in your firm's response. Your firm also did not provide documentation that it reviewed all previous complaints/feedback to ensure that they were received, reviewed, and evaluated as required. Your firm's corrective action plan does not include a time frame for implementation or any documented evidence that the feedback forms have been created or that personnel have been trained.

2. Failure to review and evaluate all complaints to determine whether an investigation is necessary and, when no investigation is made, failure to maintain a record that includes the reason why no investigation was made and the name of the individual responsible for the decision not to investigate, as required by 21 CFR 820.198(b). For example:

a. CFF #S1197 shows that Anprolene AN74ix failed the self test. The documentation does not note the cause for the malfunction.b. CFF # S1101 indicates that the Anprolene sterilizer AN74.64 failed the self-test and that a new sterilizer was sent to the customer. The reason for the failure or necessary action to prevent recurrence is not included in the documentation. The documentation is incomplete regarding investigations.

We reviewed your firm's response dated December 16, 2011, and conclude that it is not adequate. Your firm stated that the ventilation pumps complaints were treated as a known issue that was investigated in 2005 and that standard procedures were established to deal with this particular pump issue. Your firm also stated that it will create an external feedback form as an attachment to the revised feedback procedure. The form will be device specific and will include questionnaires that will assist in the preliminary root cause analysis all customer feedbacks received by your firm. In addition, your firm did not provide documentation that it reviewed all other complaints to ensure that investigations were conducted as required and, if not required, that the justification for not conducting the investigation would be documented. Your firm's corrective action plan does not include a time frame for implementation, any documented evidence that the feedback forms have been created, or evidence that personnel have been trained, and it does not address the need for investigations to be performed on complaints requiring investigation.

3. Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications; specifically, failure to develop documented instructions, standard operating procedures, and methods that define and control the manner of production, as required by 21 CFR 820.70(a). For example, thirty-one ampoules were under-filled during production of AN 3033.00, Lot 111707, on November 01, 2011. MQP 106.0, Sealing End Operation of 20 ml Ampoule Filling Machine, indicates that if the total low's reaches (b)(4) ampoules, then the supervisor is called. The procedure does not provide additional instructions necessary to correct or improve the process subsequent to calling the supervisor.

We reviewed your firm's response dated December 16, 2011, and conclude that it is not adequate. Your firm states that Quality Assurance will revise MQP106 (Sealing End Operation of 20ml Ampoule Filling Machine) and MQP112 (Sealing End Operation of 5ml Ampoule Filling Machine) to add troubleshooting instructions when too many (more than (b)(4) over-filled or under-filled ampoules are detected by the (b)(4) in-process weight inspection during a single (b)(4) shift. The instructions will specify the conditions under which production must be stopped as well as the criteria that distinguish routine adjustments from issues that require referral to the internal feedback procedure including root cause analysis, CAPA and engineering change as applicable. Your firm has a corrective action plan; however, no implementation date was provided, nor did your firm provide any revised procedures or documented evidence of training on those procedures. Additionally, your firm did not discuss the need to evaluate other production processes to determine if sufficient instructions are in place to correct and improve the process.

4. Failure to establish adequate procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22. For example, the audit schedule does not reflect the firm's entire quality system and, according to the firm's quality audit procedures, the frequency at which internal quality audits are to be conducted is once every (b)(4) There is no record of internal audits for 2009 and incomplete documentation of auditing of the quality system for 2010 and 2011. Several areas have not been audited and are not planned for audit in 2012.

We reviewed your firm's response dated December 16, 2011, and conclude that it is not adequate. Your firm indicated that its internal audit procedure QAP003 is currently being revised. Updates of the procedure include increasing the minimum audit frequency to at least one audit per procedure per (b)(4) period. The audit schedule will be reviewed to ensure coverage of the entire quality system including procedures other than manufacturing processes. Your firm did not provide a revised procedure, a quality audit plan that covers the entire quality system, evidence of the quality audit taking place, an implementation date for the corrective action, or justification for conducting an audit once per (b)(4) period.

5. Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency, as required by 21 CFR 820.20(c). For example, complaint data and service related issues are not trended and in many cases, complaints and service issues related to devices under warranty are not reported to management by the complaint handling unit. No record of management review attendees is available to show that required personnel participated in management reviews.

We reviewed your firm's response dated December 16, 2011, and conclude that it is not adequate. Your firm states that QA will revise the Feedback Response Procedure QAP034 to address feedback arising from routine service, normal wear and tear, and improper use. Feedback Response Procedure QAP034 will generate a log that will include all external feedback and categorize it by failure modes so that the frequency of each failure mode is readily visible and can be trended. QA will also revise the Management Review Procedure QAP014 to add an agenda item to the quarterly Management Review Board meetings where any negative trends of a given failure mode observed during the quarter will be reported. Additionally, a signature block will be added to the quarterly management review agenda form and all the management review board attendees will sign and date a hard copy of the management review board notes. The signed copy will be electronically scanned and used as a record of the quarterly management review board meeting. There is a corrective action plan in place; however no implementation date or documented evidence of implementation was provided. Your firm's response does not address complaint and service issues of devices under warranty not being reported to management.

Your firm's response should be sent to: Atlanta District Office, 60 Eighth Street NE, Atlanta, Georgia, 30309. If you have any questions about the contents of this letter, please contact Mr. Derek Price by phone at (404) 253-2277 or by fax (404) 253-1205.

Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm's facility. It is your firm's responsibility to ensure compliance with applicable laws and regulations administered by FDA The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality management systems. Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.